57 research outputs found
Systematic Improvement of Empirical Energy Functions in the Era of Machine Learning
The impact of targeted replacement of individual terms in empirical force
fields is quantitatively assessed for pure water, dichloromethane (DCM), and
solvated K and Cl ions. For the electrostatics, point charges (PCs) and
machine learning (ML)based minimally distributed charges (MDCM) fitted to the
molecular electrostatic potential are evaluated together with electrostatics
based on the Coulomb integral. The impact of explicitly including second-order
terms is investigated by adding a fragment molecular orbital (FMO)-derived
polarization energy to an existing force field, in this case CHARMM. It is
demonstrated that anisotropic electrostatics reduce the RMSE for water (by 1.6
kcal/mol), DCM (by 0.8 kcal/mol) and for solvated Cl clusters (by 0.4
kcal/mol). An additional polarization term can be neglected for DCM but notably
improves errors in pure water (by 1.1 kcal/mol) and in Cl clusters (by 0.4
kcal/mol) and is key to describing solvated K, reducing the RMSE by 2.3
kcal/mol. A 12-6 Lennard-Jones functional form is found to perform
satisfactorily with PC and MDCM electrostatics, but is not appropriate for
descriptions that account for the electrostatic penetration energy. The
importance of many-body contributions is assessed by comparing a strictly
2-body approach with self-consistent reference data. DCM can be approximated
well with a 2-body potential while water and solvated K and Cl ions
require explicit many-body corrections. The present work systematically
quantifies which terms improve the performance of an existing force field and
what reference data to use for parametrizing these terms in a tractable fashion
for ML fitting of pure and heterogeneous systems
Molecular Ansa-Basket: Synthesis of Inherently Chiral All-Carbon [12](1,6)Pyrenophane
The
synthesis of inherently chiral all-carbon C2-symmetric [12](1,6)pyrenophane 1 is reported. The cyclophane 1 was obtained
via a ring-closing alkyne metathesis reaction using Mortreux’s
catalyst molybdenum hexacarbonyl and 2-fluorophenol as a phenol additive.
The M and P enantiomers of the all-carbon pyrenophane 1 were demonstrated to be very stable in their enantiopure form even
upon prolonged heating at 200 °C. [12](1,6)Pyrenophane-6-yne 1 was fully characterized by high-resolution mass spectrometry,
nuclear magnetic resonance, UV–vis, and measured and calculated
electronic circular dichroism spectroscopy
Polarizable Multipolar Molecular Dynamics Using Distributed Point Charges
Distributed point charge models (DCM) and their minimal variants (MDCM) have
been integrated with tools widely used for condensed-phase simulations,
including a virial-based barostat and a slow-growth algorithm for thermodynamic
integration. Minimal DCM is further developed with a systematic approach to
reduce fitting errors in the electrostatic interaction energy and a new
fragment-based approach offers considerable speedup of the MDCM fitting process
for larger molecules with increased numbers of off-centered charged sites.
Finally, polarizable (M)DCM is also introduced in the present work. The
developments are used in condensed-phase simulations of popular force fields
with commonly applied simulation conditions. (M)DCM equivalents for a range of
widely used water force fields and for fluorobenzene (PhF) are developed and
applied along with the original models to evaluate the impact of reformulating
the electrostatic term. Comparisons of the molecular electrostatic potential
(MEP), electrostatic interaction energies, and bulk properties from molecular
dynamics simulations for a range of models from simple TIPP () to
the polarizable, multipolar iAMOEBA models for water and an existing
quadrupolar model for PhF confirm that DCMs retain the accuracy of the original
models, providing a homogeneous, efficient, and generic point charge
alternative to a multipolar electrostatic model for force field development and
multilevel simulations.Comment: 84 pages, 12 figures, journal articl
The human act of eating as the birth of the digital architecture
A conversation between the Editorial Committee members
Back to the future: asymmetrical DπA 2,2'-bipyridine ligands for homoleptic copper(I)-based dyes in dye-sensitized solar cells
Metal complexes used as sensitizers in dye-sensitized solar cells (DSCs) are conventionally constructed using a push-pull strategy with electron-releasing and electron-withdrawing (anchoring) ligands. In a new paradigm we have designed new D π A ligands incorporating diarylaminophenyl donor substituents and phosphonic acid anchoring groups. These new ligands function as organic dyes. For two separate classes of D π A ligands with 2,2'-bipyridine metal-binding domains, the DSCs containing the copper(I) complexes [Cu(D π A) 2 ] + perform better than the push-pull analogues [Cu(D D )(AA) ] + . Furthermore, we have shown for the first time that the complexes [Cu(D π A) 2 ] + perform better than the organic D π A dye in DSCs. The synthetic studies and the device performances are rationalised with the aid of density functional theory (DFT) and time-dependent DFT (TD-DFT) studies
Conversation on a Digital Follie
A Digital Folly (2021). A digital type based on experiential communication and learning above an administrative pool. This Folly is an “atmospheric screen” engaging its audience in its micro-knowledge. A sphere, a uniform solid where every point on its surface is equidistant from its center. This digital, nomadic educational society interacts under the umbrella of the digital canvas; a screen as a laboratory searching for extraordinary knowledge. This new canvas is the digital “filmine” where everything happens. The window of windows assembles open researches into a “Digital Follie”. Every window is a lab itself, and the assemblage acts as an exquisite cadaver. A lab of labs, collectively produced, searching for knowledge
On Temporality
A conversation between the Editorial Committee member
Mechanistic Insight into the Precursor Chemistry of ZrO₂ and HfO₂ Nanocrystals; towards Size-Tunable Syntheses
ne can nowadays readily generate monodisperse colloidal nanocrystals, but a retrosynthetic analysis is still not possible since the underlying chemistry is often poorly understood. Here, we provide insight into the reaction mechanism of colloidal zirconia and hafnia nanocrystals synthesized from metal chloride and metal isopropoxide. We identify the active precursor species in the reaction mixture through a combination of nuclear magnetic resonance spectroscopy (NMR), density functional theory (DFT) calculations, and pair distribution function (PDF) analysis. We gain insight into the interaction of the surfactant, tri-n-octylphosphine oxide (TOPO), and the different precursors. Interestingly, we identify a peculiar X-type ligand redistribution mechanism that can be steered by the relative amount of Lewis base (L-type). We further monitor how the reaction mixture decomposes using solution NMR and gas chromatography, and we find that ZrCl4 is formed as a by-product of the reaction, limiting the reaction yield. The reaction proceeds via two competing mechanisms: E1 elimination (dominating) and SN1 substitution (minor). Using this new mechanistic insight, we adapted the synthesis to optimize the yield and gain control over nanocrystal size. These insights will allow the rational design and synthesis of complex oxide nanocrystals
Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations
BACKGROUND
Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma.
METHODS
We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma.
RESULTS
A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group.
CONCLUSIONS
In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965.
Temporarily quadrupling the dose of inhaled steroid to prevent asthma exacerbations : FAST
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 70. See the NIHR Journals Library website for further project information.Peer reviewedPublisher PD
- …